Cost-effectiveness of Postexposure Prophylaxis After Sexual or Injection-Drug Exposure to Human Immunodeficiency VirusFREE

From the Center for AIDS Intervention Research, Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee (Dr Pinkerton); the University of California– San Francisco Positive Health Program at San Francisco General Hospital (Drs Martin, Roland, Katz, and Kahn); the Center for AIDS Prevention Studies, University of California–San Francisco (Drs Martin and Coates); and the San Francisco Department of Public Health (Dr Katz). Dr Roland has received honorarium from GlaxoSmithKline, Bristol-Myers Squibb, and Agouron Pharmaceuticals.

ABSTRACT

BackgroundThe cost-effectiveness of interventions that provide human immunodeficiency virus (HIV) postexposure prophylaxis (PEP) to individuals after sexual or injection-drug use exposures depends on the distribution of exposure routes, prevalence of infection among source partners, adherence to PEP regimens, medical care costs, and prevailing epidemiologic contexts, among other factors.

ObjectiveTo determine the cost-effectiveness of a comprehensive program to prevent HIV infection after sexual or injection-drug use exposure for 401 persons seeking PEP in an urban community.

MethodsWe conducted a retrospective cost analysis to evaluate the cost of the PEP intervention, then combined this information with model-based effectiveness estimates to determine the PEP program's "cost-utility ratio," which is the ratio of net program costs to the total number of quality-adjusted life-years (QALYs) saved by the program.

ResultsThe average cost of the PEP regimen was $1222, and the total cost of the program was $450 970. The PEP program prevented an estimated 1.26 HIV infections, saved 11.74 QALYs, and averted $281 323 in future HIV-related medical care costs. The overall cost-utility ratio was $14 449 per QALY saved. When analysis was restricted to men reporting receptive anal intercourse, the savings in averted HIV-related medical care costs exceeded the cost of the program. The results were generally robust to changes in key parameter values but were sensitive to assumptions about the HIV transmission probability for receptive anal intercourse.

Figures in this Article

Prompt initiation of a 4-week course of antiretroviral therapy soon after occupational exposure to human immunodeficiency virus (HIV) substantially reduced the risk of HIV seroconversion in a case-control study of health care workers.1 The US Public Health Service, therefore, recommends postexposure prophylaxis (PEP) with antiretroviral agents for persons with "occupational HIV exposures for which there is a recognized transmission risk."2 Although the US Public Health Service has stated that it "cannot definitively recommend for or against antiretroviral agents in [nonoccupational] situations because of the lack of efficacy data,"3 the effectiveness of PEP in the occupational setting, together with evidence of efficacy in animal model systems,4- 6 has prompted physicians in the United States and abroad to consider the use of PEP for persons potentially exposed to HIV through sexual or needle-sharing activities.7- 16 The US Public Health Service has established a registry to track nonoccupational exposures to HIV and has issued preliminary recommendations regarding the use of PEP for these exposures.3 Expert guidelines for nonoccupational PEP have been published in major medical journals.12,17 However, there are concerns about the relatively high cost of this intervention,18 especially compared with behaviorally based risk-reduction interventions.19,20

The first large-scale feasibility study21 of PEP in persons reporting sexual or injection-drug exposures was undertaken in San Francisco between December 1, 1997, and March 31, 1999. Postexposure prophylaxis with 4 weeks of antiretroviral drug treatment was provided within 72 hours to individuals who reported exposures from partners known to be infected with HIV or at risk of infection. This feasibility study demonstrated that there is demand for PEP in the community, that exposed persons can rapidly access PEP services, and that most persons administered PEP will complete the therapeutic regimen without serious adverse effects and will return for follow-up HIV antibody testing.

Preliminary modeling studies14,22- 24 of nonoccupational PEP for isolated exposures indicate that PEP is cost-effective only under certain circumstances, such as after sharing a needle or engaging in receptive (but not insertive) anal intercourse with a high-risk partner or after receptive vaginal intercourse with a partner known to be infected. Empirical evidence on the cost-effectiveness of nonoccupational PEP is lacking. The cost-effectiveness of PEP programs, as implemented, depends on (1) the mix of high-risk and lower-risk patients, (2) the proportion of individuals who complete therapy, (3) the proportion of partners known to be infected with HIV, (4) the per-exposure risk of infection, (5) the effectiveness of antiretroviral agents at blocking infection, and (6) the costs associated with the various medication regimens prescribed and laboratory tests performed. To address these uncertainties, we conducted a cost-effectiveness analysis of nonoccupational PEP using data from the San Francisco PEP program.

METHODS

We used standard techniques of cost-effectiveness analysis25- 27 to assess the cost per quality-adjusted life-year (QALY) saved by the PEP program.28 The main cost analysis was conducted from the societal perspective and, therefore, included all identifiable costs, regardless of who bore these costs. In particular, the analysis included program-related costs to patients, such as time and transportation for clinic visits, in addition to costs borne by the program itself. Future savings in averted HIV-related medical care costs and quality-of-life benefits were discounted at a 3% annual rate and expressed in year 2000 US dollars. We conducted threshold and sensitivity analyses on key parameters to assess how uncertainty in these parameters affected the main results. Table 1 summarizes the parameter values used in the base-case analysis.

PEP PROTOCOL

The San Francisco PEP study21 was designed to assess the feasibility of providing PEP for nonoccupational HIV exposures. The comprehensive protocol used in this study included several expensive, research-related components that likely would be omitted from a PEP program administered by a municipal or private health care facility, such as intensive behavioral risk-reduction counseling, extensive adherence counseling, and routine laboratory toxic reaction monitoring. The present analysis evaluates a simplified protocol (described in this subsection), based on the San Francisco study but modified to more closely represent the expected costs of community-based PEP programs.

Information about the San Francisco PEP program was disseminated through posters, flyers, and palm cards distributed at locations frequented by persons at high risk of HIV infection and through community outreach to health care providers. Prospective patients were directed to a 24-hour hotline for risk assessment and counseling. Hotline callers were counseled to help them make informed choices regarding the initiation of PEP based on the degree of risk associated with the potential HIV exposure and the HIV status or risk status of their partner. Callers who elected to initiate PEP were encouraged to go to the program clinic as soon as possible. Patients who were not able to be seen at the clinic soon thereafter were prescribed, when possible, sufficient antiretroviral medication to last until the initial clinic contact.

In the simplified protocol, the initial clinical assessment included a discussion of the potential benefits and negative consequences of PEP, a medical evaluation, brief HIV risk assessment and risk-reduction counseling, and medication adherence counseling (Table 2). Patients were asked about the HIV infection status of the exposure source, if known, and were encouraged to bring in the source partner for HIV antibody testing and counseling if his or her HIV status was unknown. Previous antiretroviral medication use and response to therapy of HIV-infected sources were obtained from patients, if possible. This information was used to craft a prophylactic antiretroviral regimen for the exposed patient to which the source's virus most likely is susceptible.32 Female patients received a pregnancy test, and all patients were tested for HIV antibodies. Patients were provided with an initial 7-day supply of antiretroviral medications and were asked to return in 1 week.

At the first follow-up visit (week 1), patients received HIV antibody test results and posttest counseling. Clinicians provided an additional 21-day supply of antiretroviral medications and reinforced the importance of strict adherence to the antiretroviral regimen. Patients were retested for the presence of HIV antibodies at weeks 12 and 26 and received test results at weeks 13 and 27. Brief HIV risk-reduction counseling was provided at all follow-up visits. In addition to these scheduled clinic visits, some patients required additional medical consultations, either by telephone or in person, to address toxic effect–related issues (Table 2).

DESCRIPTION OF SAMPLE

A total of 401 participants enrolled in the San Francisco PEP study. Table 3 gives the distribution of patients by type of exposure, percentage of patients in each exposure group who completed PEP therapy, and the proportion of completers with a known HIV-infected source.21 Patients who reported multiple exposures were classified according to the highest risk exposure. Three hundred twelve patients (78%) were known to have completed the 4-week PEP regimen; 46% of this group reported that they knew the source was infected with HIV.32 Thirty-seven participants were lost to follow-up; we assumed that they discontinued therapy. The main reasons for discontinuation were medication toxic effects (n = 27) and reassessment of risk for HIV exposure, including determination that the source partner was not infected (n = 10).21

COST ANALYSIS

Program costs were obtained from financial and other records kept by the study investigators, salary and fringe benefit information from the study clinics, information from the San Francisco General Hospital pharmacy, wholesale drug price listings, and participant questionnaires. Costs were broken down into several categories: costs associated with community outreach efforts and the development, production, and distribution of promotional materials (posters, flyers, and palm cards); telephone hotline costs (staff compensation, patient opportunity costs, and utility charges); clinic costs (clinician and staff compensation, laboratory tests, and miscellaneous supplies); antiretroviral medication costs; and opportunity costs for participants and source partners (time and transportation for clinic visits and hotline calls). The program cost estimate reflects the inclusive cost of implementing the intervention, including costs associated with telephone calls from ineligible persons and clinic and drug costs for persons who did not complete the PEP therapy.

ESTIMATING THE NUMBER OF INFECTIONS AVERTED

The number of HIV infections averted by the PEP program is the difference between the number of infections that would be expected with and without the program. For an isolated potential exposure to HIV, PEP reduces the risk of sustained infection from πα to πα(1 − E), where π is the probability that the partner or syringe is infected with HIV; α is the probability of HIV transmission associated with the particular exposure, assuming that the partner is infected; and E is the effectiveness of PEP at preventing sustained infection in the face of exposure to the virus. Thus, PEP reduces the risk of infection by πα − [πα(1 − E)]
= παE. In the present analysis, PEP was assumed to be effective only if the patient was known to have completed the regimen; no risk reduction was assumed for noncompleters or for individuals for whom follow-up information was unavailable.

In the cost-effectiveness framework, successful prevention efforts are associated with savings in QALYs and HIV-related medical care treatment costs. However, these savings are realized only if the patient does not subsequently become infected through continued risk behavior.33,34 For each patient, we estimated the long-term infection probability, L, for a 10-year period using the following equation: (1) L = 1–(1–ι)10, where ι is the annual HIV incidence for the patient's exposure group.24 The total number of infections averted, A, was obtained by calculating each patient's effective risk reduction, παE(1–L), and summing across patients. As noted previously herein, E was set to zero if the patient was not known to have completed the PEP regimen.

If the source of the exposure was known to be infected, then π was set to 1. In the San Francisco PEP program, 43% of patients reported that their partners were known to be infected with HIV; of the 28% of these partners who were brought in for testing, all were, in fact, HIV positive.21,32 For sources whose HIV status was unknown, the probability that the partner was infected (π) was set to the estimated prevalence of HIV in San Francisco among men who have sex with men, men who have sex with women, women who have sex with men, injection-drug users, or members of the general population, as appropriate.31Table 4 lists the epidemiologic parameters used in the base-case and sensitivity analyses.

Estimates of the per-exposure HIV transmission probabilities for vaginal, anal, and oral sex with an infected partner,17,36 for injecting with an infected syringe,37- 39 and for needlesticks40 were obtained from the literature. Little information is available about the probability of transmission for other exposure routes, such as mucosal exposures to semen or blood. We assumed an infection risk of 0.00004 (one-tenth the risk of the next lowest risk exposure) for these exposures.

The effectiveness of PEP using combination antiretroviral therapy for nonoccupational exposures to HIV is unknown. The baseline effectiveness estimate was inferred from the Centers for Disease Control and Prevention multinational case-control study1 that compared health care workers who received zidovudine prophylaxis after percutaneous exposure to HIV-contaminated blood with those who did not. In this study, PEP with zidovudine was associated with an 81% reduction in seroconversion risk (95% confidence interval, 48%-94%). In the base-case analysis, we assume that combination therapy after sexual or injection-drug exposure is as effective as zidovudine monotherapy after occupational exposure (ie, 81%). Although the San Francisco PEP study was not designed to evaluate effectiveness, no seroconversions occurred among patients treated with PEP during the first 6 months of follow-up.21

COST-EFFECTIVENESS AND COST-UTILITY RATIOS

The main outcome in the present analysis is the cost-utility ratio, which is the ratio of net program costs to the total number of QALYs saved by the program, where the net program cost is obtained by subtracting from the gross cost the estimated future savings in averted HIV-related medical care expenses. Symbolically, the cost-utility ratio equals (2) (C–AT)/AQ, where T and Q equal the HIV-related medical care costs and QALYs saved, respectively, per averted case of HIV infection,28,41A is the number of HIV infections averted, and C is the gross cost of the PEP program. In the QALY framework, each year of life spent in a particular health state is weighted by a factor between 0 and 1 that reflects the quality of life associated with that health state. By incorporating the impact of health programs on both morbidity and mortality, the use of QALYs in the cost-utility ratio permits comparisons across disparate areas of health care.25 Health-related programs with cost-utility ratios that are less than approximately $40 000 to $60 000 per QALY saved are generally considered cost-effective, whereas those whose cost-utility ratios exceed $180 000 to $200 000 per QALY saved are not usually considered cost-effective.28,42- 44 Society may or may not be willing to fund health-related programs with intermediate cost-utility ratios.42,45

We used the estimates of Holtgrave and Pinkerton28,29 of the number of QALYs saved by preventing someone from becoming infected, adjusted for the older age of participants in the San Francisco PEP program. According to this model, someone who becomes infected at age 32 years (the median age of participants in the San Francisco program) loses approximately 9.31 QALYs. The corresponding lifetime cost of HIV-related care is $223 072 in discounted 2000 dollars. This estimate includes approximately $13 000 per year in antiretroviral medications and more than $80 000 in AIDS treatment costs (including hospitalization). Because these estimates are somewhat outdated but more current estimates are unavailable, we subjected these parameters to extensive sensitivity and threshold analyses.

The numerator of the cost-utility ratio, C–AT, represents the difference between the total cost of the program and the amount of future HIV-related medical care savings owing to the infections prevented by the program. If this difference is negative, then the program is cost-saving overall. (This is a conservative definition of cost-saving in that it incorporates all program costs but neglects economic benefits other than savings in medical treatment costs.) In particular, the program is cost-saving only if the cost per infection averted (C/A) is less than the estimated lifetime cost of medical care for an HIV-infected individual (T = $223 072).

THRESHOLD AND SENSITIVITY ANALYSES

We conducted threshold analyses for the main parameters used in the analysis. For each parameter, we calculated the minimum or maximum values required to achieve cost-utility ratios of $0 per QALY saved (this is the cost-saving threshold), $60 000 per QALY saved (cost-effective threshold), and $200 000 per QALY saved (non–cost-effective threshold), while keeping the other parameters fixed at their base-case values. Threshold analyses also were performed to determine the total cost and number of infections averted at which the program would be cost-saving, cost-effective, or not cost-effective.

We conducted several univariate sensitivity analyses in which a single target parameter was varied continuously and 4 multivariate sensitivity analyses in which (1) all HIV transmission probabilities were set to either their highest or lowest estimated value (see Table 4), (2) the HIV incidence and prevalence values for all exposure groups were obtained from an alternative source,35 (3) the savings in QALYs and HIV-related medical care costs were varied simultaneously, or (4) alternative antiretroviral medication cost estimates were used.

RESULTS

The total cost of the PEP program was $450 970, including $226 939 (50% of the total cost) for antiretroviral medications, $146 961 (33%) for patient time and travel expenses for clinic visits, $37 831 (8%) for physician and clinical staff time, $16 586 (4%) associated with the hotline, $13 227 (3%) for promotional activities, and $9425 (2%) for laboratory testing and supplies. Patient and partner opportunity costs accounted for 34% of the total cost (including $6325 for time spent during initial calls to the hotline). The average cost per patient was $1125. The mean cost per completed PEP regimen was $1222 (vs $784 for noncompleted regimens).

In the absence of PEP, the exposures reported by the 401 patients in the PEP program would be expected to result in 2.36 infections. Use of PEP reduced the expected number of infections to 0.77 and, therefore, prevented an estimated 1.59 infections. However, approximately 21% of the 1.59 patients with averted infections would later acquire HIV as a result of continuing risk behaviors during the subsequent 10 years. Adjusting for continuing risk, the PEP program can be credited with saving the $281 323 medical care costs and the 11.74 QALYs associated with 1.26 infections. The cost-utility ratio was $14 449 per QALY saved. This ratio indicates that the PEP program was cost-effective by conventional standards.

Most of the averted infections (96%) were among men who reported exposure through receptive anal intercourse (RAI) with other men. When restricted to this subgroup, the PEP program was cost-saving: the cost per infection averted was $177 923, which is less than the estimated lifetime cost of treating HIV and AIDS. The program was moderately cost-effective for injection-drug exposures (cost-utility ratio, $86 462 per QALY saved) and possibly cost-effective for male-female RAI ($165 289 per QALY saved). The cost-utility ratio exceeded $200 000 per QALY saved for all other exposures, including nonoccupational needlesticks ($227 634 per QALY saved), receptive vaginal intercourse ($262 562 per QALY saved), and male-male insertive anal intercourse ($686 525 per QALY saved). The overall cost-utility ratio for men who reported exposure through male-male sex (receptive or insertive anal intercourse, receptive oral sex, or "other") was $8607, whereas the cost-utility ratio for all other exposures combined was $258 667 per QALY saved.

The PEP program was cost-saving for patients who reported that their partner was HIV positive (43% of the total sample), whereas for unknown status partners, the cost-utility ratio was $58 025. However, these results were mainly driven by the men who reported exposure via RAI. The cost-utility ratio was negative (cost-saving) for the 174 men who engaged in RAI with an infected male partner but $278 671 for the 93 patients who were exposed through other routes.

The results of the threshold analyses are given in Table 5. The PEP program would remain cost-effective (cost-utility ratio of $60 000 per QALY saved) for program costs up to $2458 per patient (more than twice the base-case value of $1125) or for as few as 0.58 infections averted (less than half the base-case value of 1.26). The program would be cost-saving if it averted more than 2.02 infections or cost less than $702 per patient.

In the base-case analysis we assumed that patients remained at risk of infection for 10 years after participating in the PEP program, with an annual risk equal to the incidence of infection in the associated exposure group. The cost-utility ratio remained less than $60 000 per QALY saved for up to 44 years of continued risk or for incidence rates as high as 9% in all groups (Table 5).

The results of selected univariate sensitivity analyses are illustrated in Figure 1. The program remained cost-effective when the PEP effectiveness parameter was set to 48%, the lower bound of the 95% confidence interval for zidovudine PEP effectiveness obtained in the Centers for Disease Control and Prevention case-control study.1 However, the PEP program would not be cost-saving, overall, even if the antiretroviral regimen were 100% effective at preventing infection. The program was cost-effective for PEP completion rates greater than 29%, which is substantially smaller than the rate observed in the San Francisco study (78%) and in studies of PEP after occupational exposures (59%-76%46). Moreover, the program remained cost-effective regardless of the percentage of partners known to be infected with HIV or the prevalence of infection among partners whose HIV status was unknown.

Place holder to copy figure label and caption

Cost-utility ratios (cost per quality-adjusted life-year [QALY] saved) as a function of postexposure prophylaxis (PEP) effectiveness, completion rate, proportion of partners known to be human immunodeficiency virus (HIV) infected, and HIV prevalence. In this analysis, each target parameter was varied individually, holding all other parameters at their base-case values.

The results were not sensitive to the HIV-related treatment cost and QALYs saved parameters (T and Q, respectively, in equation 2). The program was cost-effective provided that at least 2.24 QALYs were saved per averted infection and, moreover, was cost-effective regardless of the cost of treating HIV and AIDS (ie, even if treatment costs nothing). Varying T and Q conjointly, the program remained cost-effective to 46% of the base-case values of these parameters, that is, to T = $102 613 and Q = 4.28. In comparison, discounting T and Q by 5% rather than 3% decreased T and Q to $179 826 and 6.15, respectively, resulting in a cost-utility ratio of $28 905 per QALY saved. Thus, the program still would be cost-effective if a 5% discount rate were used. When a 0% discount rate was used (T = $314 018 and Q = 18.23), the cost-utility ratio decreased to $2385 per QALY saved.

The cost-utility ratio was most sensitive to the RAI transmission probability. The threshold analysis (Table 5) indicated that the PEP program would be cost-saving, overall, if this probability exceeded 0.033 and would be cost-effective (cost-utility ratio of $60 000 per QALY saved) for probabilities as small as 0.009 (the base-case value of this parameter was 0.02). Conversely, the program would not be cost-effective (cost-utility ratio >$200 000 per QALY saved) if the per-exposure transmission probability for RAI was less than 0.003. Thus, the program might or might not be considered cost-effective for transmission probabilities between 0.003 and 0.009.

As a check on the impact of our epidemiologic assumptions, we repeated the cost-effectiveness analysis using alternative, published HIV prevalence and incidence estimates for San Francisco (see Table 4).35 The resultant cost-utility ratio ($11 081 per QALY saved) was less than the base-case value calculated using estimates from the San Francisco Department of Public Health.31

We also conducted a sensitivity analysis in which all transmission probabilities were simultaneously set to their smallest or largest estimated values (Table 4). The cost-utility ratio increased to $71 381 when the transmission probabilities were set to their smallest values and decreased to less than zero (cost-saving) when they were set to their largest values.

Antiretroviral medications accounted for approximately half of the total program cost in the base-case analysis, which used the average wholesale prices listed in the Red Book of drug prices.30 The actual cost of the drugs to the PEP program was substantially less because the San Francisco General Hospital pharmacy obtains discounted prices from the pharmaceutical companies. Using these costs instead of Red Book estimates reduced the total cost of antiretroviral medications from $226 939 to $129 837 and decreased the cost-utility ratio from $14 465 to $6179 per QALY saved. We believe that the Red Book prices better reflect the current societal cost of antiretroviral drugs.

Antiretroviral regimens were individually tailored to minimize the potential for resistance. To assess the impact that particular drug regimens had on the cost-utility ratio, we reran the analysis twice, first assuming that all patients received the least expensive regimen (didanosine and stavudine) and then assuming that they received the most expensive regimen (zidovudine, lamivudine, and nelfinavir mesylate). The resulting antiretroviral cost total ranged from $191 079 to $477 855, and the cost-utility ratio ranged from $11 395 to $35 819 per QALY saved.

The PEP protocol evaluated in the base-case analysis assumed that patients received only standard risk-reduction counseling (10 minutes at each clinic visit). As an adjunctive intervention in the postexposure setting, the optimal frequency and duration of such counseling is unknown. We conducted a sensitivity analysis in which patients received an additional 15 minutes of counseling (25 minutes total) at each visit. The additional counseling increased the cost-utility ratio slightly, to $16 645 per QALY saved.

COMMENT

Previous estimates of the cost-effectiveness of hypothetical nonoccupational PEP programs suggest that PEP is cost-effective after high-risk exposures such as RAI or needle sharing with an infected partner but not after lower-risk exposures.14,22- 24 The overall cost-effectiveness of PEP in actual program settings depends on the precise mix of exposures reported by patients and the likelihood that the source partners were infected with HIV.

The present analysis indicates that a PEP program modeled after the San Francisco PEP study21 was cost-saving for men who reported RAI and possibly cost-effective for injection-drug exposures and women reporting RAI but probably was not cost-effective for other exposures. Although fewer than half of the patients reported male-male RAI, the PEP program was cost-effective overall and thus represents an economically sound use of societal health promotion resources.

The PEP program cost $14 449 per QALY saved. In comparison, the cost-utility ratios reported in a recent review47 of various preventive services ranged from cost-saving to $27 000 000 per QALY saved, with a median of $14 000 per QALY saved; in a previous study48 of the cost-effectiveness of clinical and public health measures, most of the ratios were between $10 000 and $100 000 per QALY saved. The PEP program was less cost-effective than many but more cost-effective than some behavior-based HIV risk-reduction interventions, including small-group counseling and interventions designed to change behaviors and social norms.49 The cost-effectiveness results presented herein pertain to the specific epidemiologic and sexual behavior characteristics of the study population in San Francisco. Results of the sensitivity and threshold analyses indicate that the program would remain cost-effective over a wide range of assumptions about the prevalence and incidence of HIV in the target community. Nevertheless, there may be scenarios under which PEP would not be cost-effective, such as communities in which the HIV incidence and prevalence are low or the epidemic is primarily heterosexual.

The cost-effectiveness of PEP depends on the risk associated with potential exposures. Nearly half of the patients (48%) reported male-male RAI as their highest-risk exposure. A similar percentage of patients (45%) reported male-male RAI in a study of Boston's Fenway Community Health Center PEP program.50 In the present study, the cost-utility ratio was negative for male-male RAI but was nearly $500 000 per QALY saved for all other exposures combined. We conducted a special threshold analysis to determine the smallest proportion of patients reporting male-male RAI needed to make the program cost-effective at the $60 000 per QALY saved level. This analysis indicated that the program would still be cost-effective if as few as 20% of the patients reported male-male RAI.

The results were sensitive to the per-exposure transmission probability associated with RAI. The PEP program no longer would be cost-effective if this probability were one-tenth as large (0.002), as assumed in the base-case analysis. The exact value of this critical parameter is not known with certainty. Various factors are believed to affect the per-exposure probability of HIV transmission, including infection with other sexually transmitted diseases, HIV infection stage, and reductions in genital viral load as a consequence of effective antiretroviral therapy.51

The effectiveness of PEP after sexual, injection-drug, and other nonoccupational exposures is unknown. We assumed that dual- and triple-drug PEP was as effective (81%) as zidovudine PEP was found to be in a case-control study1 of occupational exposures. The effectiveness of combination antiretroviral regimens for PEP after sexual and injection-drug exposures has not been established.3 Postexposure prophylaxis using multidrug regimens may be more effective than zidovudine PEP owing to the greater antiviral activity of these regimens. Differences in the transmission dynamics of sexual (mucosal) and occupational (percutaneous) exposures may also impact PEP effectiveness.12 In our analysis, the PEP program was cost-effective for PEP effectiveness levels as low as 38%. In contrast, the program would not be cost-saving even if PEP were completely effective (although the program would reduce the number of infections to zero, the associated savings in medical care costs would not be sufficient to offset the cost of the program).

Postexposure prophylaxis programs present numerous challenges and raise significant concerns. The greatest concern is the possibility that the availability of PEP might lead to increased sexual risk taking and that the increased risky behavior could paradoxically lead to higher rates of HIV infection.12,14,21,52,53 Another concern is that the antiretroviral agents used for PEP are incompletely suppressive and could induce resistance to the medications used to prevent HIV infection.14 This would eventually limit treatment options for patients infected with HIV. In addition, treatment with certain antiretroviral agents, such as nevirapine, used intermittently or used for multiple courses, may induce a hypersensitivity reaction.54 Other concerns include the possibility of reduced funding for behavior-based projects in favor of biologic interventions such as PEP.19,20 This would have the undesired effect of fostering competition for support among complementary programs aimed at reducing HIV infection.

The present analysis focuses on the benefits of PEP viewed as a biomedical intervention to prevent infection from a single HIV exposure. As such, it neglects additional benefits that may arise as a consequence of participation in PEP programs. Postexposure prophylaxis programs provide an excellent opportunity to engage persons whose recent behavior has placed them at risk of contracting HIV.12 After assessing their risk of acquiring HIV, these individuals are likely to be highly motivated to prevent future potential exposures. Comprehensive PEP programs that incorporate risk-reduction counseling and HIV antibody testing can capitalize on this critical time to help patients adopt safer behaviors.21 In the San Francisco PEP program, previously undiagnosed HIV infections were identified in 4 participants and 1 source partner.21,32 Identification of HIV infection benefits the patient, who can then seek appropriate medical care, and the public health, through risk-reduction measures adopted by the newly identified HIV-infected person.55 These benefits are not accounted for in our cost-effectiveness analysis, which, therefore, may be somewhat conservative.

Postexposure prophylaxis differs from traditional HIV prevention interventions that attempt to prevent exposure by attempting to block infection after exposure has occurred. Postexposure prophylaxis is not intended to supplant these proactive prevention strategies but rather to complement them.3 The results presented herein indicate that PEP can be a cost-effective component of a balanced public health portfolio of HIV prevention interventions.

This research was supported by investigator grants R01-MH55440 (Dr Pinkerton), K02-MH01919 (Dr Pinkerton), K24-MH64384 (Dr Kahn), and R01-AI42523 (Dr Coates) and center grants P30-MH52776 (Center for AIDS Intervention Research), P50-MH42459 (Center for AIDS Prevention Studies), and P30-MH59037 (University of California–San Francisco Gladstone Center for AIDS Research) from the National Institutes of Health, Bethesda, Md; and by grants CC97-0962 and CC99-SF-001 from the University of California–San Francisco AIDS Research Institute and the University of California University-wide AIDS Research Program.

Not Available, Public Health Service guidelines for the management of health-care worker exposure to HIV and recommendations for postexposure prophylaxis: Centers for Disease Control and Prevention. MMWR Recomm Rep. 1998;47
((RR-7))
1- 33PubMed

Not Available, Management of possible sexual, injecting-drug-use, or other nonoccupational exposure to HIV, including considerations related to antiretroviral therapy: Public Health Service statement: Centers for Disease Control and Prevention. MMWR Recomm Rep. 1998;47
((RR-17))
1- 14PubMed

Kahn
JG Are NEPs cost-effective in preventing HIV infections? Lurie
PReingold
ALPublic Health Impact of Needle Exchange Programs in the United States and Abroad. Berkeley School of Public Health, University of California1993;473- 509

Figures

Place holder to copy figure label and caption

Cost-utility ratios (cost per quality-adjusted life-year [QALY] saved) as a function of postexposure prophylaxis (PEP) effectiveness, completion rate, proportion of partners known to be human immunodeficiency virus (HIV) infected, and HIV prevalence. In this analysis, each target parameter was varied individually, holding all other parameters at their base-case values.

References

Not Available, Public Health Service guidelines for the management of health-care worker exposure to HIV and recommendations for postexposure prophylaxis: Centers for Disease Control and Prevention. MMWR Recomm Rep. 1998;47
((RR-7))
1- 33PubMed

Not Available, Management of possible sexual, injecting-drug-use, or other nonoccupational exposure to HIV, including considerations related to antiretroviral therapy: Public Health Service statement: Centers for Disease Control and Prevention. MMWR Recomm Rep. 1998;47
((RR-17))
1- 14PubMed

Kahn
JG Are NEPs cost-effective in preventing HIV infections? Lurie
PReingold
ALPublic Health Impact of Needle Exchange Programs in the United States and Abroad. Berkeley School of Public Health, University of California1993;473- 509

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